背景:肠道菌群对于免疫稳态至关重要,并且与慢性乙型肝炎感染的预后相关。Peyer的补丁(PP),以肠粘膜定位为特征,参与肠道微生物群介导的免疫反应。然而,PPs是否以及如何协调肠道微生物调节的抗乙型肝炎病毒(HBV)反应仍然难以捉摸。本研究旨在阐明PPs在肠道菌群介导的抗HBV适应性免疫中的作用。
方法:我们通过转录组学研究了肠道菌群和PPs对适应性免疫反应的影响,表型,和功能分析从HBV小鼠模型与肠道共生微生物群和PP消耗干预。
结果:肠道微生物群的消耗损害了系统适应性免疫反应,导致HBV抗原清除延迟。PPs的差异表达基因分析显示,与适应性免疫反应相关的途径在肠道微生物群缺陷型小鼠中显著下调。值得注意的是,PPs的消耗可以消除肠道微生物群增强肝内HBV特异性T细胞反应,导致小鼠血清乙型肝炎表面抗原水平较高。
结论:PPs协调肠道菌群介导的肝内抗HBV细胞免疫,强调远程操纵“肠道微生物群-PPs”轴对实现最佳抗HBV反应的重要性。
Gut microbiota is crucial for immune homeostasis and is associated with the prognosis of chronic hepatitis B infection. Peyer\'s patches (PPs), characterized by intestinal mucosa localization, are involved in the gut microbiota-mediated immune response. However, whether and how PPs orchestrate gut microbiota-modulated anti-hepatitis B virus (HBV) response remain elusive. This study aims to elucidate the role of PPs in gut microbiota-mediated anti-HBV adaptive immunity.
We investigated the effects of gut microbiota and PPs on adaptive immune responses by transcriptomic, phenotypic, and functional analyzes from an HBV mouse model with gut commensal microbiota and PP-depleting interventions.
Depletion of gut microbiota impaired systemic adaptive immune responses, resulting in a delayed HBV antigen clearance. Differentially expressed genes analysis of PPs revealed that pathways related to adaptive immune responses were significantly downregulated in gut microbiota-deficient mice. Notably, the depletion of PPs could abolish gut microbiota-boosted intrahepatic HBV-specific T cell response, leading to a higher serum hepatitis B surface antigen level in mice.
PPs orchestrate gut microbiota-mediated intrahepatic anti-HBV cellular immunity, underlining the significance of remote manipulating the \"gut microbiota-PPs\" axis for achieving optimum anti-HBV response.